The objectives of the proposed research plan are to elucidate the adaptative metabolic responses in the gastrointestinal and pulmonary tissues to environmental xenobiotics (i.e. environmental contaminants, occupational chemicals, cigarette smoke, dietary factors). The properties of drug metabolizing enzymes will be studied using heavy metal salts as tools in vitro. After in vitro studies, and partially parallely with them, in vivo studies on the influence of heavy metal compounds on drug metabolizing enzyme activities will be done. The influences of PCB, PBB and polychlorinated naphthalenes on the biotransformation rates will be studied and the relationship between the induction and the actual amounts of xenobiotics present in the tissues will be quantitated. The influence of cigarette smoke on the pulmonary drug and hormone metabolism as well as on the lipid metabolism will be studied. The intestinal biotransformation regulation by dietary factors, both nutritients and dietary contaminants will be further evaluated using in vitro models and isolated intestinal sacs. The steroid metabolism in the lungs will be further characterized. Moreover, the steroid metabolism in the gingiva will be studied and the influence of diseases and pregnancy and hormonal contraceptives on the gingival steroid metabolism is investigated.